The present invention relates generally to the removal of viruses from solution and, more particularly, to the preparation of immobilized cellular adsorbents used for removal of viral contaminants from blood, plasma, serum, and blood-derived products.
Viruses in blood products used for intravenous administration present well-recognized risks of infection despite health history evaluations and serological screening. Infections which have been transmitted in this manner include hepatitis and AIDS. Similarly, the presence of viruses in animal sera supplied for cell culture often results in contamination of the culture.
Numerous attempts have been made to prevent or eliminate viral contamination in solution by inactivating the viruses. However, the problems encountered in viral inactivation in blood and protein solutions are distinct from the problems of viral inactivation in other aqueous solutions. Viruses in many aqueous solutions can easily be inactivated by pasteurization, radiation and/or chemical sterilization. In contrast, whole blood, some blood protein fractions and most protein solutions such as protein-based pharmaceuticals are sensitive to such physical or chemical treatments.
Pasteurization or thermal inactivation, a widely accepted method of sterilizing certain proteins such as albumin, commonly results in a marked reduction or elimination of functional activity of labile proteins such as clotting factors. Use of high concentrations of polysaccharides to stabilize proteins during pasteurization unfortunately also increases the thermoresistance of the viruses. Viral inactivation by treatment of serum or plasma with beta-propiolactone and UV irradiation and by lipid solvent treatments results in a significant loss of functional activity of proteins.
Loss of proteins functional activity is similarly encountered when blood-based solutions are treated by hydrophobic interaction chromatography to remove the viruses from solution. Antibody-based chromatography using polyclonal antibodies and monoclonal IgM as affinity ligands preserves protein activity, but has the disadvantage of being too specific. The presence of mutants and different types of antigenic determinants thus often leads to failure of binding the target viruses. Removal of viruses from solution by filtration is also not practical because of the trade-off between required pore size restriction and the low filtrate flux.
Thus, there is a need for an improved method for removal of viral contaminants especially from blood and complex protein solutions. The present invention provides such an improved method and an adsorbent for carrying out the method. Further understanding of the invention will be had from the following disclosure taken in conjunction with the drawing and claims.